ecancer blogger Dr Bishal Gyawali rounds up the latest publications in oncology.
PCV in Glioma: not an industry-sponsored trial
It is very rare that you see the primary trial result published in JCO, but the long-term follow up results of the same trial published in NEJM. But, that’s the case with the study of adding PCV (procarbazine, CCNU and vincristine) with radiation for low-grade gliomas (LGGs) and that’s fully understandable, because the original study didn’t show any difference in survival, while this longer follow-up did.
And this is no ordinary survival difference, remember—this is one of the longest gains in OS I have ever seen with the addition of chemotherapy, a survival gain of 5.5 years with an HR of 0.59. These are the studies that make you feel good about being an oncologist and also provide optimism for a better future. Fortunately, these drugs aren’t new targeted drugs or immunotherapies so that oncologists all over the world can feel equally excited about this finding.
This paper also provides an honest and modest concluding paragraph: “Although there appears to be a small cohort of patients with grade 2 glioma who do not benefit from radiation therapy plus chemotherapy, the identification of those patients remains elusive. The magnitude of treatment benefit from combined chemotherapy plus radiation therapy is substantial, but the toxic effects are greater than those observed with radiation therapy alone. Patients and their physicians will have to weigh up whether the longer survival justifies the more toxic therapeutic approach."
In an era where a few weeks of OS extension are hailed as significant results, such modest conclusion for 5.5 years benefit provide a pleasant break. I am longing for the day when the investigators will be able to report with such modesty and honesty even for industry-funded trials. Such honesty in clinical data reporting is what all of us young oncologists should aspire to.
PET-NECK versus CUT-NECK
An important study for patients with squamous cell cancer of head and neck nodal stage N2/N3 was performed by a group with an interesting name: PET-NECK. As the name implies, they compared PET-guided image surveillance at 12 weeks post chemoradiotherapy and neck dissection only in case of incomplete or equivocal response versus planned neck dissection. They were able to demonstrate the non-inferiority for the imaging approach for the primary endpoint of OS. This approach was cost-effective with similar quality of life. Thus, especially for countries and/or patients where PET scanning is not a significant cost/logistic issue, PET-scan-based imaging post-CRT can save a lot of patients from undergoing unnecessary neck operations with no difference in survival (54/282 versus 221/282 neck surgeries in the two groups respectively).
Treatment map for mesothelioma widens with MAPS
Malignant mesothelioma can be one of the most discouraging cancer diagnoses a patient receives, with median survival below one year. This was the disease that made influential evolutionary biologist Stephen Jay Gould so hopeless that he ultimately gained courage to face eye-to-eye with cancer statistics to discover that the median was not the message (although his cancer was abdominal mesothelioma - not pleural - that we are discussing today). However, nearly half of the patients aren’t as lucky as Gould, and do succumb to this dreadful disease.
MAPS studied the addition of bevacizumab (PCB) to the standard chemotherapy cisplatin plus pemetrexed(PC) and found that the OS of patients in the PCB group was nearly 2.5 months longer (18.8 v 16.1) but at a cost of increased grade 3-4 toxicities ( 71% v 62%). Although the industry might want you to believe this as a wonderful finding, there are a few caveats for my fellow oncologists to remember before integrating these results to their own practice.
One, this phase 3 trial results are different from other phase 2 studies where they found no OS benefit to adding bevacizumab. Two, pemetrexed maintenance is usually a standard practice but was restricted to only 6 cycles in this phase 3 study. Would pemetrexed maintenace until progression provide similar benefit to adding bevacizumab? Would this benefit in OS apply to patients more than 75 years of age, excluded by this study? Is the patient happy to accept toxicities for an additional median 2.5 months survival?
Molecular profiling for lung cancer
Routine molecular profiling of tumor samples from patients with NSCLC is feasible and provides clinical benefit - this is the take-home message from a molecular profiling study by IFCT that shows that detection of genetic mutations with routine genetic profiling led to prolonged PFS and OS compared to patients without genetic mutations. However, the interpretation is not so easy here as there are many confounders to take account into. One, some mutations are not only predictive but also prognostic. NSCLC patients with EGFR mutations fare better than those without, irrespective of treatment. Next, of the detected mutations in this study, EGFR, ALK and ROS1 are already validated and routinely measured.
So, most of the survival gains could simply reflect the effect on survival due to these
mutations that already have targeted drugs and routinely used in clinical practice. A very interesting debate is presented in JAMA Oncology in this regard, with opinions offered here and here; I personally favour the view of H. Jack West without a shred of doubt.
Eribulin for sarcoma
Treatment options for sarcoma patients who relapse on anthracycline containing regimen are limited.
This phase 3 trial shows that eribulin, as compared to dacarbazine, prolongs survival by around 2 months (13.5 v 11.5) in patients with lipo-or leiomyo- sarcomas who have progressed after 2 lines of therapy including an anthracycline. It is surprising that this benefit in OS was obtained despite no difference in PFS (2.6 months in each group)-a finding opposite to that seen with most oncology treatments that prolong PFS without prolonging OS. However, this could be a characteristic of eribulin that showed similar perplexing results in trials of breast cancer. The more pertinent question would be to decide whether to use eribulin in such patients or trabectidin-a drug that improved PFS impressively (4.2 v 1.5 months) without improving OS. PS permitting, most oncologists would use both because of limited options for this disease - so the question of correct sequencing is important. This should be discussed with the patient, especially because the trials of both these drugs report treatment-related deaths.
PALOMA-3: another bevacizumab?
PALOMA-3 reports impressive PFS advantage with palbociclib plus fulvestrant versus placebo plus fulvestrant for HR HER2- metastatic breast cancer patients who progress on first-line hormone therapy. Although the data are encouraging, I am taking them with a grain of salt, given some not-so-encouraging experiences with bevacizumab and everolimus in a similar setting that failed to prolong survival later on.
Will palbociclib be another bevacizumab? Or is it really effective? I await the OS data to make any conclusions.
Coca-Cola into oncology?
Maybe someday you will be prescribing Coca-Cola to your lung cancer patients who are on PPI, as this
study shows that it leads to significant increase in bioavailability of erlotinib. I love such studies because they represent immense potential cost-reductions, if a glass of cola everyday could lower your erlotinib dose by even a little. However, who knows, cola could become unbelievably expensive soon...
Bishal Gyawali (MD) is an independent blogger. He is undergoing his postgraduate training in medical oncology at the Graduate School of Medicine, Nagoya University, Japan, where he is also a PhD candidate under the Japanese government scholarship. He also serves as visiting faculty at the department of Hemato-Oncology in Nobel Hospital, Kathamandu, Nepal. He graduated in medicine from Institute of Medicine, Tribhuwan University, Nepal in 2011 with seven gold medals for his academic excellence. He has been honoured with “Student of the Decade award” and “Best Student Award” for his academic excellence in Nepal. His areas of interest include evidence-based oncology practice, cost-effectiveness of cancer therapies and economic feasibility of cancer management in low-income countries. Dr Gyawali tweets at @oncology_bg.